|
KMID : 0578320080250010119
|
|
Molecules and Cells
2008 Volume.25 No. 1 p.119 ~ p.123
|
|
|
A Forward Genetic Approach for Analyzing the Mechanism of Resistance to the Anti-Cancer Drug, 5-Fluorouracil, Using Caenorhabditis elegans
|
|
Kim Seong-Seop
Shim Jae-Gal
|
|
|
Abstract
|
|
|
|
Pyrimidine antagonists including 5-Fluorouracil (5-FU) have been used in chemotherapy for cancer patients for over 40 years. 5-FU, especially, is a mainstay treatment for colorectal cancer. It is a pro-drug that is converted to the active drug via the nucleic acid biosynthetic pathway. The metabolites of 5-FU inhibit normal RNA and DNA function, and induce apoptosis of cancer cells. One of the major obstacles to successful chemotherapy is the resistance of cancer cells to anti-cancer drugs. Therefore, it is important to elucidate resistance mechanisms to improve the efficacy of chemotherapy. We have used C. elegans as a model system to investigate the mechanism of resistance to 5-FU, which induces germ cell death and inhibits larval development in C. elegans. We screened 5-FU resistant mutants no longer arrested as larvae by 5-FU. We obtained 18 mutants out of 72,000 F1 individuals screened, and mapped them into three complementation groups. We propose that C. elegans could be a useful model system for studying mechanisms of resistance to anti-cancer drugs.
|
|
|
KEYWORD
|
|
|
5-Fluorouracil, Anti-Cancer Drug, C. elegans, Mutant Screen, Resistance
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
  
|
|